Sugar transport and metabolism by Streptococcus mutans is directly related to the onset and development dental plaque, leading to the formation of human dental caries (tooth decay). In S. mutans, sugar substrates are taken up by ABC transporters and by phosphoenolpyruvate (PEP)-sugar phosphotransferase systems (PTSs). To better understand sugar transport and metabolism of this important dental pathogen, we have performed global transcriptional analysis of S. mutans UA159 using Expression microarrays. However, the specificity of many of these transporters has remained unknown. Since the uptake and metabolism of carbohydrates is the key step in the formation and release of cariogenic acid, it is very important to know and understand the specificity of all S. mutans sugar transporters. Therefore, the specific aim of this proposal is to: 1) identify the carbohydrate specificity of S. mutans UA159 sugar transporters using phenotype microarrays (PMs). We hypothesize that the specific sugar transporter is responsible for transport of one or more carbohydrates, and that a particular carbohydrate is transported by one, two (or more) transporters. Therefore, the results of this study will provide a library of carbon sources utilized by S. mutans, and will identify substrates for its sugar transporters. This approach is novel and innovative in that while the specificity of some individual sugar transporters in S. mutans have been studied, the substrate specificity for most of them is still unknown. Also, this is a high-throughput analysis that will allow screening of 190 different sugar substrates simultaneously. This analysis will also complement global transcriptional analysis of S. mutans sugar transporters that has been successfully accomplished in our laboratory. The information obtained from the proposed study should dramatically advance our understanding of this important human pathogen and facilitate new approaches for treatment and prevention aimed at reducing the incidence of dental caries. PUBLIC HEALTH RELEVANCE: Sugar metabolism by Streptococcus mutans is directly related to the onset and development dental plaque, leading to the formation of human dental caries (tooth decay). The uptake and metabolism of carbohydrates is the key step in the formation and release of cariogenic acid, therefore is very important to understand sugar transport of S. mutans. The results of this study will provide a library of carbon sources utilized by S. mutans, and will identify substrates for its sugar transporters. The information obtained from the proposed study should dramatically advance our understanding of this important human pathogen.